Junfei Zhou

Galanthamine, Plicamine, and Secoplicamine Alkaloids from Zephyranthes candida and Their Anti-acetylcholinesterase and Anti-inflammatory Activities

Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 μM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 μM.

Rhodomollanol A, a Highly Oxygenated Diterpenoid with a 5/7/5/5 Tetracyclic Carbon Skeleton from the Leaves of Rhododendron molle

A novel diterpenoid with an unprecedented carbon skeleton, rhodomollanol A (1), and a new grayanane diterpenoid, rhodomollein XXXI (2), were isolated from the leaves of Rhododendron molle. Their structures were elucidated using comprehensive spectroscopic methods and single-crystal X-ray diffraction. Compound 1 possesses a unique cis/trans/trans/cis/cis-fused 3/5/7/5/5/5 hexacyclic ring system featuring a rare 7-oxabicyclo[4.2.1]nonane core decorated with three cyclopentane units. The plausible biosynthetic pathway for 1 was proposed. Compound 1 exhibited moderate PTP1B inhibitory activity.

Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.

Isolation and Characterization of Sesquiterpenoids from Cassia Buds and Their Antimicrobial Activities

Cassia buds, the immature fruits of Cinnamomum cassia (Lauraceae), are widely consumed as a food spice, dietary supplements, flavoring agents, and preservatives. In this study, cassia buds were phytochemically investigated for the first time, leading to the isolation of 2 new sesquiterpenoids (1 and 2) and 10 known sesquiterpenoids (3-12). Their structures were determined by spectrometric and spectroscopic analyses, including nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and circular dichroism. Cinnamosim A (1) represents the ninth example of the rare cyperane-type sesquiterpenoids. All of the compounds (1-12) isolated from cassia buds were evaluated for antimicrobial activities, with compounds 1-3, 5-8, 11, and 12 exhibiting strong antimicrobial activities against Candida albicans and compounds 6, 7, and 11 showing moderate antibacterial activities against Escherichia coli and Staphylococcus aureus. The present investigation indicated that sesquiterpenoids from cassia buds might be used as potential antimicrobial agents to preserve food.

Rhodomollacetals A–C, PTP1B Inhibitory Diterpenoids with a 2,3:5,6-Di-seco-grayanane Skeleton from the Leaves of Rhododendron molle

Three novel diterpenoids with an unprecedented 2,3:5,6-di-seco-grayanane carbon skeleton, rhodomollacetals A-C (1-3), are isolated from the leaves of Rhododendron molle. Their structures are elucidated by comprehensive spectroscopic techniques and single-crystal X-ray diffraction. Rhodomollacetal A (1) possesses a novel cis/cis/cis/cis-fused 6/6/6/6/5 pentacyclic ring system, featuring an unprecedented 11,13,18-trioxa-pentacyclo [8.7.1.15,8.02,8.012,17]nonadecane scaffold. Compounds 2 and 3 have a rare 4-oxatricyclo[7.2.1.01,6]dodecane moiety and a 2,3-dihydro-4H-pyran-4-one unit. Compounds 1-3 showed moderate PTP1B inhibitory activities, and their molecular dockings were investigated.

Mollebenzylanols A and B, Highly Modified and Functionalized Diterpenoids with a 9-Benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane Core from Rhododendron molle

Two highly modified and functionalized diterpenoids, mollebenzylanols A (1) and B (2), and a known grayanane diterpenoid rhodojaponin III (3) were isolated from Rhododendron molle. Their structures were determined by spectroscopic data analysis, an electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis of the p-bromobenzoate ester of 1 (1a). Compounds 1 and 2 possess an unprecedented diterpene carbon skeleton featuring a unique 9-benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane core, and their plausible biosynthetic pathways are proposed. Their PTP1B inhibitory activity and modes of action were investigated.

Anti-inflammatory Grayanane Diterpenoids from the Leaves of Rhododendron molle

Thirteen new grayanane diterpenoids (1-13), a new dimeric grayanane diterpenoid, bimollfoliagein A (14), and 15 known analogues (15-29) were isolated from the leaves of Rhododendron molle. The structures of the new compounds (1-14) were determined by extensive spectroscopic data interpretation. The absolute configurations of 1-3, 7, 8, 16, 18, and 24 were defined by single-crystal X-ray diffraction analysis. Mollfoliagein A (1) represents the first example of a 2,3:11,16-diepoxy grayanane diterpenoid, featuring a cis/trans/cis/cis/trans-fused 3/5/7/6/5/5 hexacyclic ring system with a 7,13-dioxahexacyclo[10.3.3.01,11.04,9.06,8.014,17]octadecane scaffold. Diterpenoids 1-29 were evaluated for their anti-inflammatory activities in vitro, and 15, 16, 18, 19, 23-26, 28, and 29 exhibited significant inhibitory activities against nitric oxide production in lipopolysaccharide-induced RAW264.7 mouse macrophages with IC50 values ranging from 2.8 to 35.4 μM. A preliminary structure-activity relationship for the anti-inflammatory activity of diterpenoids 1-29 is discussed.

Acetylcholinesterase Inhibitory Alkaloids from the Whole Plants of Zephyranthes carinata

Eleven new alkaloids (1-11), classified as the 12-acetylplicamine (1), N-deformyl-seco-plicamine (2), plicamine (3-6), 4a-epi-plicamine (7), seco-plicamine (8), and lycorine (9-11) framework types, along with 15 known alkaloids (12-26) were isolated from the whole plants of Zephyranthes carinata. The structures of the new alkaloids 1-11 were established by extensive spectroscopic data interpretation. The absolute configurations of 9 and 10 were defined by single-crystal X-ray diffraction analysis. Zephycarinatines A (1), B (2), and G (7) represent the first examples of 12-acetylplicamine, N-deformyl-seco-plicamine, and 4a-epi-plicamine alkaloids, respectively. Alkaloids 6, 11, 17, and 20-23 exhibited AChE inhibitory activities with IC50 values ranging from 1.21 to 184.05 μM, and a preliminary structure-activity relationship is discussed.